The invention relates to a device for the preparation and measurement of a nuclear spin resonance (NMR) measurement sample, including a flow-through NMR probehead.
Nuclear spin resonance (NMR) spectroscopy is an instrumental analytical technique by which the chemical composition of measurement samples can be determined. For this, the measurement sample, which is held in a strong, static magnetic field, is subjected to high frequency (HF) pulses and the electromagnetic reaction of the sample is measured.
Liquid measurement samples are usually introduced into NMR sample tubes, and the loaded tube is transferred to the measurement location in the NMR spectrometer, mostly by the use of an automatic (e.g. pneumatic) transport apparatus. After the measurement the sample tube is removed.
Alternatively, it is possible to transport a liquid measurement sample through a system of tubes into a so-called flow-through NMR probehead. In the flow-through NMR probehead is a measurement cell, typically of larger diameter than the supply and removal tubes. The liquid measurement sample is taken from a supply volume and pumped through the tube system, usually using a transport liquid which pushes the liquid measurement sample through the tube system. After the measurement, the sample is transported out of the measurement cell. Flow-through cells for an NMR spectrometer are described, for example, in DE 10 2006 029 496 A1; a device for the transport of a liquid sample for a flow-through NMR measurement is known from DE 10 2006 023 223 B3. The measurement of liquid NMR samples using the flow-through procedure simplifies the automatic transport of the sample to the measurement location.
After measurement in accordance with the flow-through procedure, the liquid measurement sample is removed. To do this, a transport liquid (and/or the next liquid measurement sample) is pumped into the measurement cell through a tube, and the measured sample is washed out from the measurement cell through another tube and directed to an outlet. A disadvantage of this method is that after the measurement the sample is used up.
It is known from the state of the art that the signal obtained from NMR experiments can be enhanced by using a preparation of the sample, known as para-hydrogen induced polarisation (PHIP). WO 99/24080 describes a PHIP process in which para-hydrogen (pH2) is added to a symmetrical carbon-carbon double bond containing a 13C nucleus, during which spin pH2 order is transferred from pH2 to the 13C nucleus. Because the chemical structure of the measurement substance is changed by the addition of pH2, this preparation can only take place once, and, accordingly, the measurement substance is discarded after the measurement.
The post-published international patent application PCT/EP2008/004865 describes the development of a procedure by which non-equilibrium spin order from a symmetrical molecule, particularly para-hydrogen, can be transferred using simple activation measures to the hyperpolarisable nucleus of a measurement substance (compound) with the help of a template (catalyst) with sites of ordered environment, particularly a metal complex. The activation method can include, for example, the mechanical mixing of the symmetrical molecule, measurement substance and template, or the application of an alternating magnetic field to the same substances. The catalytic transfer of spin order does not change the chemical structure of the measurement substance. NMR experiments with an improved signal-to-noise ratio can be performed on the hyperpolarised nucleus.
After the activation measures, however, the spin order transferred to the measurement substance quickly decays, so that signal strength is lost even while the measurement sample is transferred to the spectrometer. Additionally, the spin order will be used up during subsequent NMR experiments, meaning that each sample can only be measured once after activation.
By measuring activated liquid measurement samples in the flow-through operation, the time between activation of the measurement sample and the beginning of the NMR measurements can be reduced, and thus more signal can be received. A measurement sample which has lost its transferred spin order as a result of an NMR experiment can also be quickly replaced by a fresh measurement sample, so that through fast, repeated NMR measurements the signal-to-noise ratio can be improved.
However, this fast replacement of the measurement sample in such a flow-through operation means that a large amount of liquid measurement sample is used up, which makes such an action rather expensive.
The object of the invention is to reduce the measurement sample consumption when doing an NMR spectroscopic measurement on liquid measurement samples to which spin order can be catalytically transferred, particularly in the manner described in PCT/EP2008/004865.